Contents lists available at ScienceDirect Drug and Alcohol Dependence journal homepage: www.elsevier.com/locate/drugalcdep Full length article Do serum markers of liver fibrosis vary by HCV infection in patients with alcohol use disorder? Arantza Sanvisens a , Alvaro Muñoz b , Ferran Bolao c , Paola Zuluaga a , Magí Farré d , Inmaculada Jarrin e , Jordi Tor a , Roberto Muga a, ⁎ a Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, IGTP, Universitat Autònoma de Barcelona, Badalona, Spain b Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA c Department of Internal Medicine, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Spain d Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, IGTP, Universitat Autònoma de Barcelona, Badalona, Spain e Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain ARTICLE INFO Keywords: Hepatitis C virus Alcohol use disorder Liver fibrosis Markers of fibrosis ABSTRACT Introduction: HCV infection is frequent in patients with alcohol use disorder (AUD). Ethanol and hepatitis C have a synergistic effect that increases the risk of end-stage liver disease. We aimed to assess fibrosis of the liver in patients admitted to treatment of AUD. Methods: Data were collected in two hospital units between 2000 and 2014. Liver fibrosis was assessed by serum biomarkers APRI, FIB-4 and Forns, and Advanced Liver Fibrosis (ALF) was defined if APRI > 1.5, FIB-4 > 3.25 or Forns > 6.9. Correlations were analyzed by Pearson’s coefficients and logistic regression models were used. Results: 1313 patients (80% M) had complete data; age at admission was 45 years (IQR: 39–52 yrs), age of initial regular alcohol consumption was 20 years (IQR: 17–26 yrs) and the amount of alcohol consumed preceding admission was 200 g/day (IQR: 120–270 g/day). Prevalence of HCV infection was 18%. Prevalence of ALF in HCV positive patients was 40.6% by APRI, 30.6% by FIB-4, and 43.3% by Forns. Correlations were high for APRI vs. FIB-4 r = 0.906, APRI vs. Forns r = 0.710, and, FIB-4 vs. Forns r = 0.825. There was no significant difference in the APRI/FIB-4 correlation by HCV status (z = 1.35, p = 0.177). However, the APRI/Forns correlation was significantly higher in HCV positive patients (p < 0.001). Patients with HCV infection were two times more likely to present with ALF at admission (OR = 2.1, 95%CI:1.5–3.1). Conclusions: HCV infection is associated with severity of fibrosis in patients with excessive alcohol consumption. In this context, APRI and FIB-4 are highly correlated which facilitates the assessment of liver damage. 1. Introduction Excessive alcohol consumption is the third leading cause of pre- mature death in western countries, and cirrhosis of the liver accounts for approximately 1%–2% of all deaths in Europe. Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur (Shoreibah et al., 2014; Singal et al., 2011). In fact, alcohol and HCV infection are the leading causes of end-stage liver disease and the most common indication for liver transplant in the US and Europe (Zakhari, 2013). AUD has been associated with a greater exposure to HCV infection, with an increased risk of viral persistence, and with more extensive damage of the liver. A recent systematic review of 24 studies found that the average prevalence of HCV infection among patients with AUD was 16.3% (Novo-Veleiro et al., 2013). The combined effect of HCV infec- tion and ethanol consumption in humans affects various host cells and has been associated with alterations in the modulation of Reactive Oxygen Species production, in the lipopolysaccharide signaling pathway, and in cytokine production; these molecular alterations eventually generate an environment of hepatocellular injury that will impair the normal antiviral immune responses and activation of cell proliferation (Szabo et al., 2010). Besides HCV infection, alcoholic liver disease (ALD) represents a spectrum of liver damage that begins with fatty liver changes in the majority of individuals who participate in excessive alcohol consump- tion. In this context, up to 20–40% of heavy drinkers will develop https://doi.org/10.1016/j.drugalcdep.2018.04.008 Received 2 February 2018; Received in revised form 6 April 2018; Accepted 10 April 2018 ⁎ Corresponding author at: Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain. E-mail address: rmuga.germanstrias@gencat.cat (R. Muga). Abbreviations: AUD, alcohol use disorder; HCV, hepatitis C virus; ALD, alcoholic liver disease; APRI, Aspartate aminotransferase/Platelet Ratio Index; AST, aspartate aminostransferase; ALT, alanine aminotransferase; GGT, gamma glutamil transferase; ALF, advanced liver fibrosis; IQR, Inter Quartile Range; OR, odds ratio Drug and Alcohol Dependence 188 (2018) 180–186 Available online 16 May 2018 0376-8716/ © 2018 Elsevier B.V. All rights reserved. T